This research aims to investigate the application of medical biotechnology with regard to the detection and treatment of hospital-associated infection. Various strategies focused on the implementation of biological detection agents and biotherapeutics are discussed, with particular emphasis placed on surface-anchoring technologies. This thesis is presented in the alternative format, consisting of published research papers embedded within the text. An extended introduction precedes each publication and a reflective commentary accompanies each research paper. For the purpose of continuity, all figure captions and references are in keeping with the body of the text.Part A concerns the detection of residual sources of transmissible infection, via the utilisation of an enzymatic detection agent, capable of modelling clinical surface contamination post sterilisation. Chapter 1 details the development of a current clinical biosensor, focused on modification of polymeric substrates via plasma activation. Covalent immobilisation facilitated enhanced proteinaceous surface retention, alongside retention of biological activity, potentially providing a more stringent assessment of hospital sterilisation measures. Chapter 2 (unpublished) investigates the possibility of protein engineering for further development of the aforementioned biosensor. This research focuses on genetic modification of the detection agent and subsequent covalent conjugation to a fluorescent reporting system, with the intention of quantifying surface contamination in the clinical setting. Part B focuses on the development of potential biological therapeutics for the treatment of infection. Chapter 3 aims to provide the theoretical background to the proceeding research in the form of a review paper. Chapter 4 concerns the utilisation of surface-anchored, polymeric nanoparticles as delivery vectors for bacteriophage, facilitating the controlled delivery of the antimicrobial cargo at an elevated temperature associated with chronic wound infection. Chapter 5 is presented as an extension of the preceding research, detailing the use of a synergistic enzybiotic cocktail as oppose to bacteriophage, in an attempt to alleviate certain regulatory concerns.
|Date of Award||30 Oct 2017|
|Sponsors||Public Health England|
|Supervisor||Toby Jenkins (Supervisor)|